Ranking the Impact of Human Health Disorders on Gut Metabolism: Systemic Lupus Erythematosus

Ranking the impact of human health disorders on gut metabolism: Systemic lupus erythematosus and obesity as study cases

David Rojo, Arancha Hevia, Rafael Bargiela, Patricia López, Adriana Cuervo, Sonia González, Ana Suárez, Borja Sánchez, Mónica Martínez-Martínez, Christian Milani, Marco Ventura, Coral Barbas, Andrés Moya, Antonio Suárez, Abelardo Margolles, Manuel Ferrer

Supplementary table legends

Supplementary Table 1 Demographics and clinical features of the SLE patients.

Supplementary Table 2 Summarized general and disease characteristics of the SLE patients and HC individuals. Full details for each subject are provided in Supplementary Table 3.

Supplementary Table 3 Detailedcharacteristics of the SLE patients and HC individuals.BMI values are included.Numerical code for column “Health”: 0, excellent; 1, good; 2, normal; 3, regular; 4, bad.Numerical code for column “Smoke”: 0, no smoke; 1, smoker; 2, ex-smoker.

Supplementary Table 4 List of raw and statistically (designated as ST) significant masses identified and quantified in a metabolome-wide scan of gut microbiota. For differential quantitative metabolomics, we compared the metabolomes of samples by evaluating peak areas from chromatographic peaks. A list of masses identified by LC-MS using positive and negative polarities and CE-MS following alignment are presented for SLE vs. HC and for HC low (HCl) vs. high (HCh) BMI. The technique (LC-MS positive (+) or negative (-) mode or CE-MS), mass error (in ppm), retention time (RT; as ppm@RT), the p value calculated using Mann-Whitney U test or t-test (denoted “pt-test or Mann-Whitney U test”) followed by Bonferroni corrections (designated “p Bonf), and the abundance level per sample (SLE or HC) and per group of samples (average [X] for “HC”, “SLE”, “HCh”, or “HCl” groups) are shown. Statistically significant differences (p values) per metabolite identified, and pairwise comparisons among mean values (abundance levels) are provided.Panel abbreviations and content as follows: LC+ raw, LC- raw, and CE raw, list of masses identified in LC-MS using positive (+) and negative (-) polarities and CE-MS, respectively, following alignment; LC+ ST SLE vs. HC, LC- ST SLE vs. HC, and CE ST SLE vs. HC, list of differential/statistically significant masses identified in LC-MS using positive and negative polarities and CE-MS, respectively, in the SLE patients compared with HC subjects; LC+ ST HCh vs. HCl, LC- ST HCh vs. HCl, and CE ST HCh vs. HCl, list of differential/statistically significant masses identified in LC-MS using positive and negative polarities and CE-MS, respectively, in the HCh subjects compared with HCl subjects.

Supplementary Table 5 List of putatively identified (ID) masses of molecules that achieved statistical criteria (Supplementary Table 4) and were responsible for samples/groups separations. The technique (LC-MS positive (+) or negative (-) mode or CE-MS), experimental mass (designated “Mass”), retention time (RT), theoretical mass (designated “Designated mass”), mass error (in ppm), putative name and formula, p values calculated using Mann-Whitney U test or t-test (denoted “pt-test or Mann-Whitney U test”) followed by Bonferroni corrections (designated “p Bonf), and the abundance level per sample (SLE or HC) and per group of samples (average[X] for “HC”, “SLE”, “HCh”, or “HCl” groups) are presented.Panel abbreviations and content as follows: LC+ ID SLE vs. HC, LC- ID SLE vs. HC, and CE ID SLE vs. HC, list of putatively identified masses in LC-MS using positive (+) and negative (-) polarities and CE-MS, respectively, that significantly differed in the SLE patients compared with HC subjects; LC+ ID HCh vs. HCl, LC- ID HCh vs. HCl, and CE ID HCh vs. HCl, list of putatively identified masses in LC-MS using positive and negative polarities and CE-MS, respectively, that were significantly different in the HCh subjects compared with HCl subjects.

Supplementary Table 1 Demographics and clinical features of the SLE patients.

Total SLE patients* / n=18
Age at diagnosis, median yearts (IQR) / 35.00 (15.00)
Disease duration, median years (IQR) / 7.00 (9.00)
Clinical manifestations, n (%)
Malar rash / 9 (50.0)
Discoid lesions / 6 (33.3)
Photosensitivity / 14 (77.8)
Oral ulcers / 9 (50.0)
Arthritis / 10 (55.6)
Serositis / 3 (16.7)
Renal disorder / 3 (16.7)
Neurological disorder / 0 (0.0)
Haematological disorder / 9 (50.0)
Anti-dsDNA, n (%) / 9 (50.0)
Titer, median U/ml (IQR) / 10.35 (36.45)

*dsDNA: double stranded DNA; IQR: interquartile range

Supplementary Table 2 Summarized general and disease characteristics of the SLE patients and HC individuals. Full details for each subject are provided in Supplementary Table 3.

SLE patients
(n=18) / HC subjects
(n=17)
Female sex (%) / 100 / 100
Age (year)(mean ± sd) / 49.1 ± 9.7 / 48.5 ± 8.0
Smokers (%) / 29 / 24
Habitual alcohol consumers (%) / 35 / 59
Regular physical activity (%) / 35 / 59
Compsumption of fermented foods (%) / 12 / 35
Use of vitamins and mineral supplements (%) / 18 / 41

Supplementary Table 3 Detailedcharacteristics of the SLE patients and HC individuals.BMI values are included. Numerical code for column “Health”: 0, excellent; 1, good; 2, normal; 3, regular; 4, bad. Numerical code for column “Smoke”: 0, no smoke; 1, smoker; 2, ex-smoker.

Supplementary Table 3 cont.Detailedcharacteristics of the SLE patients and HC individuals.BMI values are included. Numerical code for column “Health”: 0, excellent; 1, good; 2, normal; 3, regular; 4, bad. Numerical code for column “Smoke”: 0, no smoke; 1, smoker; 2, ex-smoker.